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Drought is an occurrence that brings about significant changes to the structure of areas. Its influence is especially noticeable in important regions with dry and semi-dry weather patterns, leading to a range of difficulties including interruptions in food distribution systems, lack of water, health problems, economic declines, increased migration, and inadequate energy supply. The Ardabil plain, located in Asia and the northern-western region of Iran, plays a pivotal role in crop productions within an arid environment and holds significant political importance for the country. The main objective of this study is to enhance environmental sustainability in this critical and vulnerable region, particularly in anticipation of imminent droughts. The study focuses on examining the financial impacts on agriculture and selection a crop using the SWAT model, HWA method and climate scenarios under the RCP8.5 pathway for the future period (2040–2050). Results for the near future indicate a notable decline in rainfall of around 38 %, a reduction in wheat production by approximately 25 %, and an increase in temperature of around 30 %. At present, the Ardabil Plain produces a total of 284,182 tons of wheat, with 204,980 tons from irrigated crops and 79,202 tons from rain-fed crops. However, the projected future scenario indicates a decrease in total wheat production to 202,926 tons, with 153,855 tons from irrigated crops and 49,071 tons from rain-fed crops. This decline in production is expected to lead to a total net income loss of approximately -$139,372,437, with -$87,690,344 attributed to irrigated crops and -$51,682,092 to rain-fed crops. The comprehensive hierarchy of crop choices yielded by the HWA method is outlined as follows: barley holds a superior position, followed by wheat, soybeans, and potatoes. The study findings suggest that the availability of water sources in certain regions may prompt a shift in farming land from the north to the south of the plain to promote environmental sustainability.

Ardabil Plain, which holds significant political and economic importance in agricultural production in Iran, has faced various challenges including climate change, economic sanctions, and limited access to global trade. Ensuring food security has become a key priority for the region. The main objective of this research is to identify a suitable crop for this critical region with regard to future climate change conditions. This study employs a new framework of the system dynamics model (SDM) and the Hybrid Weighted Averaging (HWA) method to assess the Water–Energy–Food (WEF) nexus and resource sustainability in the Ardabil Plain under different climate change scenarios (RCP 2.6, RCP 4.5, and RCP 8.5). The research addresses current and future water challenges, emphasizing the need for additional energy and selecting optimal crops. Using the SDM, the study analyzes the impact of water supply fluctuations on agriculture, economic gain, and energy consumption from 2021 to 2050. The results indicate that barley is the most suitable crop for the Ardabil Plain in the near future, based on the overall ranking derived from the HWA method, which is as follows: barley > wheat > soybeans > potatoes > pears. The study highlights the significant challenges in energy supply for agriculture due to declining water levels and the increased force required by pumps to supply water to farms. These findings provide valuable insights for policymakers and stakeholders to make informed decisions in addressing water scarcity and rising energy demands in the Ardabil Plain.

Objective(s): Pulmonary arterial hypertension (PAH) is a severe and often fatal disease that is associated with oxidative stress and inflammation. Alamandine, a component of the renin-angiotensin system, known for its antioxidative, anti-inflammatory, and antifibrotic effects, has been investigated in this study to determine if it has protective effects against PAH induced by monocrotaline (MCT) and if these effects are associated with oxidative stress, inflammatory factors, and inducible nitric oxide synthase (iNOS).Materials and Methods: Rats were administered MCT (40 mg/kg) on day 0 and then received alamandine (50 mg/kg/day) via mini-osmotic pumps for 21 days starting one day later. Hemodynamic parameters, electrocardiograms, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), inflammatory cytokines (TNF-α, IL-1β, and NF-κB), iNOS, and MrgD receptor expression in lung tissue were evaluated at the end of the 21-day period. The MrgD receptor was quantified through immunofluorescent staining, and the histopathology of lung tissues was evaluated using hematoxylin and eosin staining. Results: The results showed that alamandine treatment significantly improved hemodynamic parameters, oxidative stress markers, inflammatory factors, and electrocardiographic data. Furthermore, treatment with alamandine decreased the levels of iNOS. Additionally, alamandine treatment decreased the expression levels of MrgD receptors in the lung tissue of MCT-induced PAH. Conclusion: In summary, this study indicates that alamandine has protective effects against monocrotaline-induced PAH, and these effects may be attributed to the inhibition of oxidative stress, inflammatory parameters, and iNOS.

Abstract Biodegradable microparticles are useful vehicles for the controlled release of bioactive molecules in drug delivery, tissue engineering and biopharmaceutical applications. We developed dexamethasone (Dex) encapsulation into tyramine-substituted hyaluronic acid microparticles (Dex-HA-Tyr Mp) mediated by horseradish peroxidase (HRP) crosslinking using a microfluidic device and infollowing crosslinked gelatin (Gela) with proanthocyanidin (PA) as a semi-confined bed hydrogel for the repair of sciatic tissue injury. It was found that the simultaneous use of Dex-HA-Tyr Mp and cross-linked Gela-PA hydrogel improved the physical properties of the hydrogel, including mechanical strength and degradability. The designed composite also provided a sustained release system for Dex delivery to the surrounding sites, demonstrating the applicability of the fabricated hydrogel composite for sciatic nerve tissue engineering and regeneration. The encapsulated cells were viable and showed adequate growth ability and morphogenesis during prolonged incubation in Gela-PA/HA-Tyr Mp hydrogel compared to control conditions. Interestingly, histological analysis revealed a significant increase in the number of axons in the injured sciatic nerve following treatment with Dex-HA-Tyr Mp and injectable Gela-PA hydrogel compared to other control groups. In conclusion, the results demonstrated that fabricated Dex-loaded MPs and injectable hydrogel from biomimetic components are suitable systems for sustained delivery of Dex with adequate biocompatibility and the approach may have potential therapeutic applications in peripheral nerve regeneration. Graphical Abstract

Abstract Background This study aimed to evaluate the protective effects of alamandine, a new member of the angiotensin family, against doxorubicin (DOX)-induced nephrotoxicity in rats. Methods Rats were intraperitoneally injected with DOX (3.750 mg/kg/week) to reach a total cumulative dose of 15 mg/kg by day 35. Alamandine (50 µg/kg/day) was administered to the rats via mini-osmotic pumps for 42 days. At the end of the experiment, rats were placed in the metabolic cages for 24 h so that their water intake and urine output could be measured. After scarification, the rats’ serum and kidney tissues were collected, and biochemical, histopathological, and immunohistochemical studies were carried out. Results DOX administration yielded increases in pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, pro-fibrotic proteins transforming growth factor-β (TGF-β), pro-inflammatory transcription factor nuclear kappa B (NF-κB), kidney malondialdehyde (MDA), creatinine clearance, blood urea nitrogen (BUN), and water intake. On the other hand, the DOX-treated group exhibited decreased renal superoxide dismutase (SOD), renal glutathione peroxidase (GPx) activity, and urinary output. Alamandine co-therapy decreased these effects, as confirmed by histopathology and immunohistochemical analysis. Conclusions The results suggest that alamandine can prevent nephrotoxicity induced by DOX‎ in rats.

Objective: Isoproterenol (ISO)-induced heart failure is a standardized model for the study of beneficial effects of various drugs. Both apelin and angiotensin 1-7 have a cardiac protective effect. We assumed that co-therapy with apelin and angiotensin 1-7 (Ang (1-7)) may have synergistic cardioprotective effects against isoproterenol-induced heart failure. Methods The animals were randomly assigned to one of eight groups of seven animals in each group as follows: (1) control I (saline; IP injection) (1) control II (saline; via mini-osmotic pump) (3) ISO (5 mg/ kg; IP), (4) Apelin (20μg/ kg; IP), (5) Ang (1-7) (30 μg/kg/day; via mini-osmotic pump), (6) Apelin+ISO, (7) Ang (1-7)+ISO, (8) Apelin+Ang (1-7)+ISO. Rat myocardial injury was induced by intraperitoneal injection of 5mg/kg of ISO for ten days. Apelin and Ang (1-7) were administered 30 minutes before ISO injection. Results: A decrease in systolic blood pressure (SBP; p

Background & Objective: The parabrachial nucleus is a critical link in the transmission of short latency nociceptive information to midbrain neurons. GABA(A) receptors have bidirectional roles in controlling nociception and are abundant in the parabrachial region . We examined the effects of bilateral intra parabrachial microinjection of different doses of the GABA(A) receptor agonist, muscimol, and the GABA(A) receptor antagonist, bicuculline, on pain modulation using a tail-flick test . Materials & Methods: Rats were anaesthetized with sodium pentobarbital (55 mg/kg) and then special cannulas were inserted stereotaxically into the parabrachial nucleus. After 1 week of recovery, the effects of microinjection of muscimol, (62.5, 125,250 ng/side) or bicuculline, (50,100,200 ng/side) into the parabrachial on tail flick latencies were assessed. Tail-flick latencies were measured for 60 minutes every 5 min after drug microinjection. Results: Microinjection of muscimol (62.5, 125 ng/side) and bicuculline (50,100,200 ng/side) into the parabrachial did not have any statistically significant effect on tail-flick latency. Administration of, muscimol, (250 ng/side) produced thermal hyperalgesia (P

Background & Objective: The parabrachial nucleus is a critical link in the transmission of short latency nociceptive information to midbrain neurons. GABA(A) receptors have bidirectional roles in controlling nociception and are abundant in the parabrachial region . We examined the effects of bilateral intra parabrachial microinjection of different doses of the GABA(A) receptor agonist, muscimol, and the GABA(A) receptor antagonist, bicuculline, on pain modulation using a tail-flick test . Materials & Methods: Rats were anaesthetized with sodium pentobarbital (55 mg/kg) and then special cannulas were inserted stereotaxically into the parabrachial nucleus. After 1 week of recovery, the effects of microinjection of muscimol, (62.5, 125,250 ng/side) or bicuculline, (50,100,200 ng/side) into the parabrachial on tail flick latencies were assessed. Tail-flick latencies were measured for 60 minutes every 5 min after drug microinjection. Results: Microinjection of muscimol (62.5, 125 ng/side) and bicuculline (50,100,200 ng/side) into the parabrachial did not have any statistically significant effect on tail-flick latency. Administration of, muscimol, (250 ng/side) produced thermal hyperalgesia (P